Fat oxidation, hormonal and plasma metabolite kinetics during a submaximal incremental test in lean and obese adults

This study aimed to compare fat oxidation, hormonal and plasma metabolite kinetics during exercise in lean (L) and obese (O) men. Sixteen L and 16 O men [Body Mass Index (BMI): 22.9 ± 0.3 and 39.0 ± 1.4 kg · m(-2)] performed a submaximal incremental test (Incr) on a cycle-ergometer. Fat oxidation rates (FORs) were determined using indirect calorimetry. A sinusoidal model, including 3 independent variables (dilatation, symmetry, translation), was used to describe fat oxidation kinetics and determine the intensity (Fat(max)) eliciting maximal fat oxidation. Blood samples were drawn for the hormonal and plasma metabolite determination at each step of Incr. FORs (mg · FFM(-1) · min(-1)) were significantly higher from 20 to 30% of peak oxygen uptake (VO2peak) in O than in L and from 65 to 85% VO2peak in L than in O (p ≤ 0.05). FORs were similar in O and in L from 35 to 60% VO2peak. Fat max was 17% significantly lower in O than in L (p<0.01). Fat oxidation kinetics were characterized by similar translation, significantly lower dilatation and left-shift symmetry in O compared with L (p<0.05). During whole exercise, a blunted lipolysis was found in O [lower glycerol/fat mass (FM) in O than in L (p ≤ 0.001)], likely associated with higher insulin concentrations in O than in L (p<0.01). Non-esterified fatty acids (NEFA) were significantly higher in O compared with L (p<0.05). Despite the blunted lipolysis, O presented higher NEFA availability, likely due to larger amounts of FM. Therefore, a lower Fat(max), a left-shifted and less dilated curve and a lower reliance on fat oxidation at high exercise intensities suggest that the difference in the fat oxidation kinetics is likely linked to impaired muscular capacity to oxidize NEFA in O. These results may have important implications for the appropriate exercise intensity prescription in training programs designed to optimize fat oxidation in O

Connectivity Between Posterior Parietal Cortex and Ipsilateral Motor Cortex Is Altered in Schizophrenia

Background: Recent advances have highlighted the hypothesis of schizophrenia as a disorder causing defective connectivity among distinct cortical regions. Neurophysiological evidence supporting this hypothesis, however, is still lacking. Methods: In the present study, we used a novel twin-coil transcranial magnetic stimulation (tcTMS) approach to investigate ipsilateral parieto-motor connectivity in 20 schizophrenic patients (14 medicated, 6 unmedicated) and in 15 healthy age-matched volunteers. Results: In healthy subjects, a conditioning TMS pulse applied over the ipsilateral posterior parietal cortex (PPC) at 90% of resting motor threshold (RMT) intensity was able to increase the excitability of the hand area of the right primary motor cortex, with peaks at interstimulus intervals (ISIs) of 4 and 15 msec. This paradigm of stimulation failed to reveal any facilitatory parieto-motor interaction in medicated and unmedicated schizophrenic patients. The between-group difference in paired-pulse facilitation was not ISI-specific. In following analyses, we found that the effects across ISIs induced by PPC conditioning at 90% RMT correlated with the Global Assessment Functioning score and with the negative subscale of the Positive and Negative Syndrome Scale, showing that patients with a better global functioning and lower negative symptoms had less impaired connectivity. Moreover the same parameter correlated with illness duration. Conclusions: Parieto-motor connectivity is impaired in schizophrenia. Cortico-cortical disconnection might be a core feature of schizophrenia

Surgical and non surgical treatment

OBJECTIVES This contribution aims to update the dentist on some important knowledge about cancer of the mouth, particularly on the surgical, medical and radiotherapy treatment in a multidisciplinary approach. MATERIALS AND METHODS The material reported here represents the most up-to-date data on the subject, in a sort of a summary of the indications found in the medical literature and the experience of operators engaged on a daily basis in the treatment of head and neck cancer patients. RESULTS As already reported in the previous Modules of this ECM Course, the neoplasms of the head and neck area, and of the oral cavity in particular, represent aggressive diseases, burdened by 50% of loco- regional recurrences or distant metastases. For this reason, their treatment requires an initial collaboration between surgeon, oncologist and radiotherapist. Moreover, there are many other figures who play a crucial role in the overall management of these patients. The choice of the optimal treatment option, in the single patient, has recently become more difficult in consideration of the different possibilities that derive from the advances in surgery, radiotherapy and medical treatment: only a multidisciplinary approach is able to offer the right treatment in the right patient. It is now widely known that carcinoma of the posterior third of the tongue that is HPV-positive (Human Papilloma Virus, HPV) has a better response to treatment if radiotherapy is provided, and better overall survival when compared with HPV-negatives case. Radiotherapy (RT) has become an integral part of the multidisciplinary approach and frequently accompanies the fundamental therapeutic strategy still represented by surgery. The adoption of Intensity Modulated Radiation Therapy (IMRT) has reformed the approach to oral cancer. IMRT has been shown to improve accuracy towards tumor tissue, reducing the involvement of surrounding healthy tissues, leading to lower general toxicities. Surgical intervention in the most advanced cases always requires large excisions followed by reconstructions with loco-regional flaps or free microvascular flaps. It is always necessary, when anatomicalpossibilit\ue0 ly possible, to provide a margin of at least 1 cm of clinically healthy tissue and, in any case, intraoperative sections of frozen tissue allow to obtain confirmation of free margins. The optimal reconstructive option is represented by free microvascular flaps, which offer the best results obtainable in relation to speech and swallowing functions. With regard to medical therapy, cetuximab is one of the few drugs authorized for use in head-neck neoplasms. It is a monoclonal antibody, targeting Epidermal Growth Factor Receptor (EGFR), whose efficacy when used alone is rather modest. Other agents, such as cisplatin or 5-fluorouracil, which interfere with cell division, often used in combination with cetuximab increase responses. CONCLUSIONS The function of the multidisciplinary team in head-neck tumours is to bring together different healthcare professionals whose goal is to improve the prognosis and quality of life of patients. There are numerous clinical researches that testify to the advantages of this approach. Surgeons, radiotherapists and oncologists must be involved but also other figures (speech therapists, dieticians, psychologists, dentists\u2026 whose role will be described in the next Module). CLINICAL SIGNIFICANCE Only a multidisciplinary approach, with a careful initial assessment of the stage of the disease and of the psycho-physical conditions of the patient, is able to obtain the best possible results in the case of malignant neoplasms of the oral cavity and of the head-neck district

Clinical outcomes and prognostic factors in recurrent and/or metastatic head and neck cancer patients treated with chemotherapy plus cetuximab as first-line therapy in a real-world setting

Aim: The aims of the study are to evaluate the clinical outcomes of first-line treatment with platinum-based chemotherapy and cetuximab in patients with relapsing/metastatic head and neck cancer (RM HNC) and to identify predictors of treatment response. Methods: This is a retrospective, observational, longitudinal, real-world study involving 6 oncology centres in Italy. All consecutive patients with RM HNC treated between January 2007 and December 2016 with a first-line therapy consisting of a platinum-based chemotherapy regimen plus cetuximab were included. The primary objective of the study was to assess overall survival (OS) and progression-free survival (PFS). Secondary objectives included the identification of predictors of treatment response. Results: Overall, 297 patients were identified. Median OS was 10.8 months (95% confidence interval [CI] 9.3–12.2), whereas median PFS was 4.8 months (95% CI 4.3–5.5). On multivariable analysis, independent unfavourable prognostic factors for OS were performance status (PS) Eastern Cooperative Oncology Group (ECOG) >0, presence of residual tumour at primary site, platinum resistance and lack of objective response. Unfavourable predictors for PFS included cancer primary site (paranasal sinuses, hypopharynx), PS ECOG >0, presence of residual tumour at primary site, platinum resistance and lack of objective response. Independent unfavourable predictors of objective response were tumour site (oral cavity, larynx-hypopharynx), residual tumour at primary site and prior chemotherapy. Conclusions: The availability of new treatment modalities and epidemiological changes make the periodic reassessment of prognostic factors of great relevance to guide clinical practice and the design of future randomised clinical trials

DETERMINANTS OF 6-MONTH MORTALITY IN SURVIVORS OF MYOCARDIAL-INFARCTION AFTER THROMBOLYSIS - RESULTS OF THE GISSI-2 DATA-BASE

none647Background. Current knowledge of risk assessment in survivors of myocardial infarction is largely based on data gathered before the advent of thrombolysis. It must be determined whether and to what extent available information and proposed criteria of prognostication are applicable in the thrombolytic era. Methods and Results. We reassessed risk prediction in the 10 219 survivors of myocardial infarction with follow-up data available (ie, 98% of the total) who had been enrolled in the GISSI-2 trial, relying on a set of prespecified variables. The 3.5% 6-month all-cause mortality rate of these patients compared with the higher value of 4.6% found in the corresponding GISSI-1 cohort, originally allocated to streptokinase therapy, indicates a 24% reduction in postdischarge 6-month mortality. On multivariate analysis (Cox model), the following variables were predictors of 6-month all-cause mortality: ineligibility for exercise test for both cardiac (relative risk [RR], 3.30; 95% confidence interval [CI], 2.36-4.62) and noncardiac reasons (RR, 3.28; 95% CI, 2.23-4.72), early left ventricular failure (RR, 2.41; 95% Cl, 1.87-3.09), echocardiographic evidence of recovery phase left ventricular dysfunction (RR, 2.30; 95% CI, 1.78-2.98), advanced (more than 70 years) age (RR, 1.81; 95% Cl, 1.43 -2.30), electrical instability (ie, frequent and/or complex ventricular arrhythmias) (RR, 1.70; 95% Cl, 1.32-2.19), late left ventricular failure (RR, 1.54; 95% Cl, 1.17-2.03), previous myocardial infarction (RR, 1.47; 95% CI, 1.14-1.89), and a history of treated hypertension (RR, 1.32; 95% Cl, 1.05-1.65). Early post-myocardial infarction angina, a positive exercise test, female sex, history of angina, history of insulin-dependent diabetes, and anterior site of myocardial infarction were not risk predictors. On further multivariate analysis, performed on 8315 patients with the echocardiographic indicator of left ventricular dysfunction available, only previous myocardial infarction was not retained as an independent risk predictor. Conclusions. A decline in 6-month mortality of myocardial infarction survivors, seen within 6 hours of symptom onset, has been observed in recent years. Ineligibility for exercise test, early left ventricular failure, and recovery-phase left ventricular dysfunction are the most powerful (RR, >2) predictors of 6-month mortality among patients recovering from myocardial infarction after thrombolysis. Qualitative variables reflecting residual myocardial ischemia do not appear to be risk predictors. The lack of an independent adverse influence of early post-myocardial infarction angina on 6-month survival represents a major difference between this study and those of the prethrombolytic era.noneVOLPI A; DEVITA C; FRANZOSI MG; GERACI E; MAGGIONI AP; MAURI F; NEGRI E; SANTORO E; TAVAZZI L; TOGNONI G; FERUGLIO GA; LOTTO A; ROVELLI F; SOLINAS P; TAVAZZI L; TOGNONI G; BRUNO M; CAPPELLO T; COPPINI A; FINCATI F; MANTOVANI G; PANGRAZZI J; POGNA M; TURAZZA FM; ANSELMI M; BARBONAGLIA L; BIGI R; CAVALLI A; FRIGERIO M; GIORDANO A; GUALTIEROTTI C; TORTA D; CAROLA R; GIORDANO F; BARLOTTI R; LOPARCO G; VIGLINO GL; RUGGERI G; GIAMUNDO L; DANESI A; PACIARONI E; GAMBINI C; URBANO G; PURCARO A; FRANCESCONI M; FIGLIOLIA S; CANNONE M; ANTOLINI R; DEVOTI G; CRISTALLINI P; PORCIELLO PI; TEONI P; BURALI A; ZUCCONELLI V; DEMATTEIS C; IERVOGLINI A; SCATASTA M; AMABILI S; CARATTI CA; ZOLA G; FERRAGUTO P; SALICI G; CENTARO A; ROTIROTI D; GENOVESE M; GINEVRINO P; DAMATO N; ALTAMURA CM; COLONNA L; CASTELLANETA G; BOVENZI F; MESSINA D; GALANTINO A; CAMPOREALE N; CUCCHINI F; CAMPOSTELLA L; MALACRIDA R; GENONI M; PELLEGRINI P; BRIDDA A; RIGGI L; ACONE L; MOSCATIELLO G; BRUNO A; INVERNIZZI G; TESPILI M; GUAGLIUMI G; CASARI A; ALBANO T; TOMASSINI B; TORTA D; DIBIASE G; SCARAMUZZINO G; RUGGERO S; BRACCHETTI D; DECASTRO U; FULVI M; BRAITO E; ERLICHER A; OBERLECHNER W; GAGLIARDI RS; BIGHIGNOLI L; BONIZZATO G; RIZZI GM; SCAZZINA L; PERRINI A; STRANEO G; STRANEO U; SCIRE A; VERRIENTI A; GUADALUPI M; STORELLI A; ZUCCA L; DABUSTI M; ALBONICO B; DEPETRA V; TABACCHI GC; SCERVINO R; MEREU D; MAXIA P; BIANCO A; CRABU E; MANGIAMELI S; CENTAMORE G; MALFITANO D; AMICO C; VANCHERI F; SANTOPUOLI G; BALDINI F; PANTALEONI A; CONTESSOTTO F; TERLIZZI R; MERIGHI A; TURCHI E; TEGLIO V; PIGNATTI F; PEZZANA A; GOZZOLINO G; GIGLIO M; PETTINATI G; IEVA M; CIRICUGNO S; CORREALE E; ROMANO S; DIFUCCIA A; CASTELLANO B; NATALE A; CERNETTI C; CELEGON L; CANDELPERGHER G; ARIENZO F; RUSSO F; DEVIVO L; MAY L; ACHILLI G; BLASI A; SORRENTINO F; DATO A; GALLONE P; PALUMBO C; DELLAMONICA R; PAGANO L; ALBERTI A; ORSELLI L; DEPONTI C; PARMIGIANI ML; FERRARI M; ACITO P; BUSI F; DELLAVITTORIA G; BELLET C; BORTOLINI F; ROSSI A; CORONA C; BONDI S; NICCOLINI D; GAMBERI G; ARCURI G; MAIOLINO P; CARROZZA A; DELIO U; CAPRETTI G; MARINONI C; GUASCONI C; SONNINO S; PAGLIEI M; FERRARI G; LOMBARDI R; AGNELLI D; DERINALDIS G; CALCAGNILE A; SIGNORELLI S; BENDINELLI S; LUSETTI L; MOLLAIOLI M; COSMI F; PLASTINA F; VENNERI N; FERACO E; CATELLI P; POLUZZI C; DISTANTE S; BIANCHI C; COPPETTI S; ZAMPAGLIONE G; GATTO C; ZURLO R; USLENGHI E; MARGARIA F; MILANESE U; LOMANTO B; ZIACCHI V; RIVA D; BERTOCCHI P; TIRELLA G; DAULERIO M; SAURO G; BINI A; MAZZONI V; POGGI P; MARESTA A; JACOPI F; PATRONCINI A; PUPITA F; GAGGI S; FRAUSINI G; ANTONIOLI GE; MALACARNE C; CODECA L; CAPPATO R; ANDREOLI L; VARACCA S; BUIO E; FAZZINI PF; PUCCI P; SARRO F; VERGASSOLA R; BARCHIELLI M; DEMATTEIS D; CARRONE M; BRUNOZZI LT; MENICONI L; LIBERATI R; RADOGNA M; TALLONE M; CONTE R; IERI A; ZIPOLI A; SANSONI M; CANZIANI R; GUIDALI P; CRISTALLO E; MARIELLO F; MUZIO L; BENVENUTO MR; BALDINI MR; VECCHIO C; CHIARELLA F; FALCIDIENO M; CECCHI A; GIULIANO G; SEU V; PERUGINI P; TOSELLI A; BASSO F; CORTI E; ROSSI P; DELFINO R; CAPONNETTO S; GNECCO G; GHIGLIOTTI G; PENNESI A; LOMBARDI G; RUGGIERI A; BERTOLO L; SLOMP L; LANZETTA T; MAZZARONE L; CRESTI A; BELLODI G; ZUARINI AM; VENERI L; PARCHI C; GIOVANELLI N; NEGRONI S; DETHOMATIS M; BARGHINI A; MARINO E; RICCI D; LEMME P; DIGIACOMO U; AQUARO G; RONZANI G; OTTELLO B; VONTI V; MORETTI S; PALERMO R; MARSILI P; SIDERI F; RAGAZZINI G; GRAMENZI S; BATTISTINI S; DIODATO T; VALERIO A; TUCCI C; DEPASQUALE B; GELFO PG; BERTULLA A; BOLLINI R; DEMARCHI E; BACCA F; DEGIORGI V; LOCATELLI V; SAVOIA MT; FERRACINI C; BARBARESI F; COTOGNI A; FRANCO G; ROMANO S; PASSONI F; DURBANO M; MORETTI G; PEROTTI S; CAPRETTI M; DELBENE P; CASCONE M; BALDINI U; ORLANDI M; ODDONE A; CAIZZI V; MASINI G; LAZZARI M; BALLERINI B; BOZZI L; MOCETTI T; BERTOLINI A; PASOTTI E; SANGUINETTI M; MANTOVANI R; TOGNOLI T; MAGGI A; TUSA M; CAMERONI E; GUERRA GP; REGGIANI A; REDAELLI S; GIUSTI S; TANTALO L; RIZZI A; DIGIOVANNI N; GUZZO V; GABRIELE M; COLOMBO G; ALBERZONI A; SALVIOLI G; GALFETTI F; DOVICO E; BELLUZZI F; GOLA E; CASELLATO F; LECCHI G; CONSOLO F; SACCA CB; CONSOLO A; PICCOLO E; GASPARINI G; DEVITA C; ALBERTI A; MASSA D; BELLI C; DOSSENA MG; CORSINI C; SANNA GP; AZZOLLINI M; TRUAZZA F; LOTTO A; NADOR F; DEMARTINI M; BOZZI G; SEREGNI R; PASTINE I; MORPURGO M; CASAZZA F; REGALIA F; MAGGIOLINI S; RIGO R; PANCALDI S; POZZETTI D; PASCOTTO P; FRANCESCHI L; DAINESE F; MELINI L; CAPPELLI C; BERNARDI C; PALMIERI M; BORGIONI L; ZILIO G; SANDRI R; ALITTO F; MASARO G; VALAGUSSA F; SCHIAVINA R; RAVESI D; DANIELLO L; PIANTADOSI FR; BARRA P; ROMEO D; MININNI N; SEVERINO S; MOSTACCI M; CASTELLARI M; BANDA D; ROLANDI R; VILLA WD; CARBONE V; ALLEGRI M; FASCIOLO L; PITTALIS M; MUREDDU V; SORO F; DELEDDA MG; MARRAS E; MARCHI SM; DELUCA C; MANETTA M; VOLTA SD; SPERANDEO V; DONZELLI M; VITRANO MG; GERACI E; PITROLO F; LAMONICA S; BELLANCA G; MESSINA G; MIRTO U; RAINERI A; TRAINA M; DIBENEDETTO A; RIBAUDO E; DIFRANCESCO M; RONCHITELLI R; CARONE M; DIGREGORIO D; DIPAOLO G; PASQUALE M; COREA L; COCCHIERI M; ALUNNI G; PAPI L; CHIRIATTI G; LUPETTI M; GAZZOLA U; ARRUZZOLI S; VILLANI GQ; MELLINI M; MADRUZZA L; PIAZZA R; MICHELI G; FRANCHINI C; BECHI S; MARTINES C; MARCHESE D; GABBIA G; BIGALLI A; CIUTI M; CABANI E; DELCITERNA F; ALFIERI A; CHITI M; LONGHINI J; CODELUPPI P; NEGRELLI M; ZANUTTINI D; NICOLOSI GL; MARTIN G; PETRELLA A; BARDAZZI L; BIANCO GA; CELLAMARE G; GIANNELLI F; LICITRA G; LICITRA R; LETTICA GV; TUMIOTTO G; BELLANTI G; BOSI S; CASALI G; MONDUCCI I; BARONE A; PARENTI F; HEYMAN J; COZZI E; BALDACCI G; BACCOS D; BRIGHI F; DESANCTIS A; BOCK R; PALMIERI M; ROSSI F; AMATI P; SEMPRINI P; NARDELLI A; BOTTERO G; VARTOLO C; MILAZZOTTO F; DICROCE G; DIMARIO F; ANGRISANI G; AZZOLINI P; NEJA CP; MANZOLI U; ROSSI E; TRANI C; MASINI V; SEBASTIANI F; TOPAI M; BORGIA MC; LUCIANI C; FERRI F; DEPAOLA D; CAPURSO S; TUGNOLI F; VETTA C; ALTIERI T; BORZI M; VISCOMI A; STRIANO U; SALITURI S; ZONZIN P; FIORENCIS R; BADIN A; RAVERA B; BALDI C; SILVESTRI F; ALLEMANO P; REYNAUD S; SANSON A; MILANI L; DESIMONE MV; RUSSO A; VILLELLA A; GRAZINI M; AMIDEI S; ANSELMI L; PICCANICOLINO R; MASCELLI G; TAGLIAMONTE A; MESSINA V; TEDESCHI C; BOSSI M; BISIOLI M; TACCHI G; PAGNI G; VIVALDI F; IBBA GV; SANNIA L; PEDRAZZINI F; BAGNI E; FABII S; ALVINO A; ANTONIELLI E; DORONZO B; MARTINENGO E; BECCHI G; SALMOIRAGHI A; DIGIOVANNA F; CARAMANNO G; CAPORICCI D; BRUN M; GIANI P; FERRARIO G; PECI P; RONCONI G; SKOUSE D; BIANCHI C; GIUSTINIANI S; CUCCHI GF; TAVASCI E; SILVERII A; MARCELLINI G; SPECA G; STANISCIA D; CIMINO A; SERAFINI N; DEBONIS P; CERRUTI P; BAZZUCCHI M; DALPRA F; SPEROTTO C; MOLE GD; BARBANO G; POMARI F; GASCHINO G; PARIGI A; GANDOLFO N; RONDONI F; BRUSCA A; DILEO M; GOLZIO PG; ABRATE M; SCLAVO MG; ROCCI R; POGGIO G; GIANI S; CUZZUCREA D; BRASCHI GB; SCIACCA R; SAMMARTANO A; FURLANELLO F; BRAITO G; CUZZATO V; TOTIS O; FAURETTO F; LEO F; GALATI A; PALMA P; CAMERINI F; MORGERA T; BARBIERI L; FERUGLIO GA; SLAVICK GA; FRESCO C; CUDA A; SARNICOLA P; ARZILLO P; BINAGHI G; MACCHI G; CALVERI G; DIMARCO G; LEVANTESI G; PANERAI C; CATURELLI G; FACCHIN L; SARTORE G; ZARDINI P; MARINO P; CARBONIERI E; NAVA S; MAZZINI C; NAVA R; SERRA N; SASSARA M; NICROSINI F; GANDOLFI P; BERGOGNONI G; BALLESTRA AM; VIOLO CVOLPI A; DEVITA C; FRANZOSI MG; GERACI E; MAGGIONI AP; MAURI F; NEGRI E; SANTORO E; TAVAZZI L; TOGNONI G; FERUGLIO GA; LOTTO A; ROVELLI F; SOLINAS P; TAVAZZI L; TOGNONI G; BRUNO M; CAPPELLO T; COPPINI A; FINCATI F; MANTOVANI G; PANGRAZZI J; POGNA M; TURAZZA FM; ANSELMI M; BARBONAGLIA L; BIGI R; CAVALLI A; FRIGERIO M; GIORDANO A; GUALTIEROTTI C; TORTA D; CAROLA R; GIORDANO F; BARLOTTI R; LOPARCO G; VIGLINO GL; RUGGERI G; GIAMUNDO L; DANESI A; PACIARONI E; GAMBINI C; URBANO G; PURCARO A; FRANCESCONI M; FIGLIOLIA S; CANNONE M; ANTOLINI R; DEVOTI G; CRISTALLINI P; PORCIELLO PI; TEONI P; BURALI A; ZUCCONELLI V; DEMATTEIS C; IERVOGLINI A; SCATASTA M; AMABILI S; CARATTI CA; ZOLA G; FERRAGUTO P; SALICI G; CENTARO A; ROTIROTI D; GENOVESE M; GINEVRINO P; DAMATO N; ALTAMURA CM; COLONNA L; CASTELLANETA G; BOVENZI F; MESSINA D; GALANTINO A; CAMPOREALE N; CUCCHINI F; CAMPOSTELLA L; MALACRIDA R; GENONI M; PELLEGRINI P; BRIDDA A; RIGGI L; ACONE L; MOSCATIELLO G; BRUNO A; INVERNIZZI G; TESPILI M; GUAGLIUMI G; CASARI A; ALBANO T; TOMASSINI B; TORTA D; DIBIASE G; SCARAMUZZINO G; RUGGERO S; BRACCHETTI D; DECASTRO U; FULVI M; BRAITO E; ERLICHER A; OBERLECHNER W; GAGLIARDI RS; BIGHIGNOLI L; BONIZZATO G; RIZZI GM; SCAZZINA L; PERRINI A; STRANEO G; STRANEO U; SCIRE A; VERRIENTI A; GUADALUPI M; STORELLI A; ZUCCA L; DABUSTI M; ALBONICO B; DEPETRA V; TABACCHI GC; SCERVINO R; MEREU D; MAXIA P; BIANCO A; CRABU E; MANGIAMELI S; CENTAMORE G; MALFITANO D; AMICO C; VANCHERI F; SANTOPUOLI G; BALDINI F; PANTALEONI A; CONTESSOTTO F; TERLIZZI R; MERIGHI A; TURCHI E; TEGLIO V; PIGNATTI F; PEZZANA A; GOZZOLINO G; GIGLIO M; PETTINATI G; IEVA M; CIRICUGNO S; CORREALE E; ROMANO S; DIFUCCIA A; CASTELLANO B; NATALE A; CERNETTI C; CELEGON L; CANDELPERGHER G; ARIENZO F; RUSSO F; DEVIVO L; MAY L; ACHILLI G; BLASI A; SORRENTINO F; DATO A; GALLONE P; PALUMBO C; DELLAMONICA R; PAGANO L; ALBERTI A; ORSELLI L; DEPONTI C; PARMIGIANI ML; FERRARI M; ACITO P; BUSI F; DELLAVITTORIA G; BELLET C; BORTOLINI F; ROSSI A; CORONA C; BONDI S; NICCOLINI D; GAMBERI G; ARCURI G; MAIOLINO P; CARROZZA A; DELIO U; CAPRETTI G; MARINONI C; GUASCONI C; SONNINO S; PAGLIEI M; FERRARI G; LOMBARDI R; AGNELLI D; DERINALDIS G; CALCAGNILE A; SIGNORELLI S; BENDINELLI S; LUSETTI L; MOLLAIOLI M; COSMI F; PLASTINA F; VENNERI N; FERACO E; CATELLI P; POLUZZI C; DISTANTE S; BIANCHI C; COPPETTI S; ZAMPAGLIONE G; GATTO C; ZURLO R; USLENGHI E; MARGARIA F; MILANESE U; LOMANTO B; ZIACCHI V; RIVA D; BERTOCCHI P; TIRELLA G; DAULERIO M; SAURO G; BINI A; MAZZONI V; POGGI P; MARESTA A; JACOPI F; PATRONCINI A; PUPITA F; GAGGI S; FRAUSINI G; ANTONIOLI GE; MALACARNE C; CODECA L; CAPPATO R; ANDREOLI L; VARACCA S; BUIO E; FAZZINI PF; PUCCI P; SARRO F; VERGASSOLA R; BARCHIELLI M; DEMATTEIS D; CARRONE M; BRUNOZZI LT; MENICONI L; LIBERATI R; RADOGNA M; TALLONE M; CONTE R; IERI A; ZIPOLI A; SANSONI M; CANZIANI R; GUIDALI P; CRISTALLO E; MARIELLO F; MUZIO L; BENVENUTO MR; BALDINI MR; VECCHIO C; CHIARELLA F; FALCIDIENO M; CECCHI A; GIULIANO G; SEU V; PERUGINI P; TOSELLI A; BASSO F; CORTI E; ROSSI P; DELFINO R; CAPONNETTO S; GNECCO G; GHIGLIOTTI G; PENNESI A; LOMBARDI G; RUGGIERI A; BERTOLO L; SLOMP L; LANZETTA T; MAZZARONE L; CRESTI A; BELLODI G; ZUARINI AM; VENERI L; PARCHI C; GIOVANELLI N; NEGRONI S; DETHOMATIS M; BARGHINI A; MARINO E; RICCI D; LEMME P; DIGIACOMO U; AQUARO G; RONZANI G; OTTELLO B; VONTI V; MORETTI S; PALERMO R; MARSILI P; SIDERI F; RAGAZZINI G; GRAMENZI S; BATTISTINI S; DIODATO T; VALERIO A; TUCCI C; DEPASQUALE B; GELFO PG; BERTULLA A; BOLLINI R; DEMARCHI E; BACCA F; DEGIORGI V; LOCATELLI V; SAVOIA MT; FERRACINI C; BARBARESI F; COTOGNI A; FRANCO G; ROMANO S; PASSONI F; DURBANO M; MORETTI G; PEROTTI S; CAPRETTI M; DELBENE P; CASCONE M; BALDINI U; ORLANDI M; ODDONE A; CAIZZI V; MASINI G; LAZZARI M; BALLERINI B; BOZZI L; MOCETTI T; BERTOLINI A; PASOTTI E; SANGUINETTI M; MANTOVANI R; TOGNOLI T; MAGGI A; TUSA M; CAMERONI E; GUERRA GP; REGGIANI A; REDAELLI S; GIUSTI S; TANTALO L; RIZZI A; DIGIOVANNI N; GUZZO V; GABRIELE M; COLOMBO G; ALBERZONI A; SALVIOLI G; GALFETTI F; DOVICO E; BELLUZZI F; GOLA E; CASELLATO F; LECCHI G; CONSOLO F; SACCA CB; CONSOLO A; PICCOLO E; GASPARINI G; DEVITA C; ALBERTI A; MASSA D; BELLI C; DOSSENA MG; CORSINI C; SANNA GP; AZZOLLINI M; TRUAZZA F; LOTTO A; NADOR F; DEMARTINI M; BOZZI G; SEREGNI R; PASTINE I; MORPURGO M; CASAZZA F; REGALIA F; MAGGIOLINI S; RIGO R; PANCALDI S; POZZETTI D; PASCOTTO P; FRANCESCHI L; DAINESE F; MELINI L; CAPPELLI C; BERNARDI C; PALMIERI M; BORGIONI L; ZILIO G; SANDRI R; ALITTO F; MASARO G; VALAGUSSA F; SCHIAVINA R; RAVESI D; DANIELLO L; PIANTADOSI FR; BARRA P; ROMEO D; MININNI N; SEVERINO S; MOSTACCI M; CASTELLARI M; BANDA D; ROLANDI R; VILLA WD; CARBONE V; ALLEGRI M; FASCIOLO L; PITTALIS M; MUREDDU V; SORO F; DELEDDA MG; MARRAS E; MARCHI SM; DELUCA C; MANETTA M; VOLTA SD; SPERANDEO V; DONZELLI M; VITRANO MG; GERACI E; PITROLO F; LAMONICA S; BELLANCA G; MESSINA G; MIRTO U; RAINERI A; TRAINA M; DIBENEDETTO A; RIBAUDO E; DIFRANCESCO M; RONCHITELLI R; CARONE M; DIGREGORIO D; DIPAOLO G; PASQUALE M; COREA L; COCCHIERI M; ALUNNI G; PAPI L; CHIRIATTI G; LUPETTI M; GAZZOLA U; ARRUZZOLI S; VILLANI GQ; MELLINI M; MADRUZZA L; PIAZZA R; MICHELI G; FRANCHINI C; BECHI S; MARTINES C; MARCHESE D; GABBIA G; BIGALLI A; CIUTI M; CABANI E; DELCITERNA F; ALFIERI A; CHITI M; LONGHINI J; CODELUPPI P; NEGRELLI M; ZANUTTINI D; NICOLOSI GL; MARTIN G; PETRELLA A; BARDAZZI L; BIANCO GA; CELLAMARE G; GIANNELLI F; LICITRA G; LICITRA R; LETTICA GV; TUMIOTTO G; BELLANTI G; BOSI S; CASALI G; MONDUCCI I; BARONE A; PARENTI F; HEYMAN J; COZZI E; BALDACCI G; BACCOS D; BRIGHI F; DESANCTIS A; BOCK R; PALMIERI M; ROSSI F; AMATI P; SEMPRINI P; NARDELLI A; BOTTERO G; VARTOLO C; MILAZZOTTO F; DICROCE G; DIMARIO F; ANGRISANI G; AZZOLINI P; NEJA CP; MANZOLI U; ROSSI E; TRANI C; MASINI V; SEBASTIANI F; TOPAI M; BORGIA MC; LUCIANI C; FERRI F; DEPAOLA D; CAPURSO S; TUGNOLI F; VETTA C; ALTIERI T; BORZI M; VISCOMI A; STRIANO U; SALITURI S; ZONZIN P; FIORENCIS R; BADIN A; RAVERA B; BALDI C; SILVESTRI F; ALLEMANO P; REYNAUD S; SANSON A; MILANI L; DESIMONE MV; RUSSO A; VILLELLA A; GRAZINI M; AMIDEI S; ANSELMI L; PICCANICOLINO R; MASCELLI G; TAGLIAMONTE A; MESSINA V; TEDESCHI C; BOSSI M; BISIOLI M; TACCHI G; PAGNI G; VIVALDI F; IBBA GV; SANNIA L; PEDRAZZINI F; BAGNI E; FABII S; ALVINO A; ANTONIELLI E; DORONZO B; MARTINENGO E; BECCHI G; SALMOIRAGHI A; DIGIOVANNA F; CARAMANNO G; CAPORICCI D; BRUN M; GIANI P; FERRARIO G; PECI P; RONCONI G; SKOUSE D; BIANCHI C; GIUSTINIANI S; CUCCHI GF; TAVASCI E; SILVERII A; MARCELLINI G; SPECA G; STANISCIA D; CIMINO A; SERAFINI N; DEBONIS P; CERRUTI P; BAZZUCCHI M; DALPRA F; SPEROTTO C; MOLE GD; BARBANO G; POMARI F; GASCHINO G; PARIGI A; GANDOLFO N; RONDONI F; BRUSCA A; DILEO M; GOLZIO PG; ABRATE M; SCLAVO MG; ROCCI R; POGGIO G; GIANI S; CUZZUCREA D; BRASCHI GB; SCIACCA R; SAMMARTANO A; FURLANELLO F; BRAITO G; CUZZATO V; TOTIS O; FAURETTO F; LEO F; GALATI A; PALMA P; CAMERINI F; MORGERA T; BARBIERI L; FERUGLIO GA; SLAVICK GA; FRESCO C; CUDA A; SARNICOLA P; ARZILLO P; BINAGHI G; MACCHI G; CALVERI G; DIMARCO G; LEVANTESI G; PANERAI C; CATURELLI G; FACCHIN L; SARTORE G; ZARDINI P; MARINO P; CARBONIERI E; NAVA S; MAZZINI C; NAVA R; SERRA N; SASSARA M; NICROSINI F; GANDOLFI P; BERGOGNONI G; BALLESTRA AM; VIOLO

MEDICAL SCIENCE. GISSI-2: A factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12 490 patients with acute myocardial infarction

A multicentre, randomised, open trial with a 2 x 2 factorial design was conducted to compare the benefits and risks of two thrombolytic agents, streptokinase (SK, 1\ub75 MU infused intravenously over 30-60 min) and alteplase (tPA, 100 mg infused intravenously over 3 h) in patients with acute myocardial infarction admitted to coronary care units within 6 h from onset of symptoms. The patients were also randomised to receive heparin (12 500 U subcutaneously twice daily until discharge from hospital, starting 12 h after beginning the tPA or SK infusion) or usual therapy. All patients without specific contraindications were given atenolol (5-10 mg iv) and aspirin (300-325 mg a day). The end-point of the study was the combined estimate of death plus severe left ventricular damage. 12 490 patients were randomised to four treatment groups (SK alone, SK plus heparin, tPA alone, tPA plus heparin). No specific differences between the two thrombolytic agents were detected as regards the combined end-point (tPA 23\ub71%; SK 22\ub75%; relative risk 1\ub704, 95% Cl 0\ub795-1\ub713), nor after the addition of heparin to the aspirin treatment (hep 22\ub77%, no hep 22\ub79%; RR 0\ub799, 95% Cl 0\ub791-1\ub708). The outcome of patients allocated to the four treatment groups was similar with respect to baseline risk factors such as age, Killip class, hours from onset of symptoms, and site and type of infarct. The rates of major in-hospital cardiac complications (reinfarction, post-infarction angina) were also similar. The incidence of major bleeds was significantly higher in SK and heparin treated patients (respectively, tPA 0\ub75%, SK 1\ub70%, RR 0\ub757, 95% Cl 0\ub738-0\ub785; hep 1\ub70%, no hep 0\ub76%, RR 1\ub764, 95% Cl 1\ub709-2\ub745), whereas the overall incidence of stroke was similar in all groups. SK and tPA appear equally effective and safe for use in routine conditions of care, in all infarct patients who have no contraindications, with or without post-thrombolytic heparin treatment. The 8\ub78% hospital mortality of the study population (compared with approximately 13% in the control cohort of the GISSI-1 trial) indicates the beneficial impact of the proven acute treatments for AMI. \ua9 1990